Mano Roy, Zilber Sofia, Di Natale Renzo G, Kedar Daniel, Lifshitz David A, Yossepowitch Ofer, Baniel Jack, Margel David
Department of Urology, Rabin Medical Center, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Pathology, Shaare Zedek Medical Center, Jerusalem, Israel; Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Urol Oncol. 2018 Dec;36(12):531.e9-531.e17. doi: 10.1016/j.urolonc.2018.09.007. Epub 2018 Oct 15.
High-grade nonmuscle-invasive urothelial tumors of the bladder that fail intravesical Bacillus Calmette-Guérin (BCG) immunotherapy are at the highest risk of progression. Initial evidence links heat shock protein expression levels and outcome of bladder cancer after BCG treatment. We aimed to determine the association between HSP60, 70, and 90 expression levels and long-term outcomes of T1 high-grade (T1HG) urothelial bladder tumors treated with BCG immunotherapy.
Data of 54 consecutive patients with primary T1HG bladder tumors who underwent transurethral resection between 2002 and 2008 and received at least an induction course of BCG were reviewed. Immunohistochemical staining for heat shock protein (HSP)60, 70, and 90 were performed on resected specimens. Study outcomes included disease recurrence and progression. The association between HSP expression levels and outcomes were evaluated with univariable and multivariable Cox proportional hazards models.
During a median follow-up of 9.6 years, 25 patients had a disease recurrence and 14 patients a disease progression. Estimated 5-year recurrence and progression-free survival were 59% and 81%, respectively. On multivariable analyses, HSP60 staining >65% was associated with a higher risk for progression (hazard ratio [HR] = 3.96, 95% confidence interval [CI] 1.35-11.58, P = 0.012), and HSP70 staining >5% was associated with a decreased risk for progression (HR = 0.33, 95% CI 0.11-0.98, P = 0.045), and recurrence (HR = 0.29, 95% CI 0.13-0.65, P = 0.003). HSP90 expression was not associated with disease recurrence or progression. Five patients had both a HSP60 staining >65% and a HSP70 staining ≤5% all of whom recurred at a median time of 6 months (interquartile range 3, 16) and 80% of whom progressed at a median time of 26 months (interquartile range 5, 60).
HSP60 and 70 cellular expression levels are associated with long-term outcome following BCG treatment of T1HG urothelial bladder tumors. These findings, if further validated, may be used to better stratify the risk of disease recurrence and progression in this group of patients.
膀胱高级别非肌层浸润性尿路上皮肿瘤若卡介苗（BCG）膀胱内免疫治疗失败，其进展风险最高。初步证据表明热休克蛋白表达水平与BCG治疗后膀胱癌的预后相关。我们旨在确定热休克蛋白60、70和90表达水平与接受BCG免疫治疗的T1期高级别（T1HG）尿路上皮膀胱肿瘤长期预后之间的关联。
回顾了2002年至2008年间连续54例接受经尿道切除术且至少接受过一个疗程BCG治疗的原发性T1HG膀胱肿瘤患者的数据。对切除标本进行热休克蛋白（HSP）60、70和90的免疫组化染色。研究结局包括疾病复发和进展。采用单变量和多变量Cox比例风险模型评估HSP表达水平与结局之间的关联。
在中位随访9.6年期间，25例患者出现疾病复发，14例患者出现疾病进展。估计5年无复发和无进展生存率分别为59%和81%。多变量分析显示，HSP60染色>65%与更高的进展风险相关（风险比[HR]=3.96，95%置信区间[CI]1.35 - 11.58，P=0.012）；HSP-70染色>5%与较低的进展风险相关（HR=0.33，95%CI 0.11 - 0.98，P=0.045）以及复发风险相关（HR=0.29，95%CI 0.13 - 0.65，P=0.003）。HSP90表达与疾病复发或进展无关。5例患者HSP60染色>65%且HSP70染色≤5%，所有这些患者均在中位时间6个月（四分位间距3, 16）复发，其中80%在中位时间26个月（四分位间距5, 60）进展。
HSP60和70细胞表达水平与BCG治疗T1HG尿路上皮膀胱肿瘤后的长期预后相关。这些发现若能进一步得到验证，可用于更好地对该组患者疾病复发和进展的风险进行分层。
